Multiple myeloma is a malignant plasma cell cancer that is increasing in frequency in today's aging population. While new combination therapies have improved the outcome of treatment, many patients fail to achieve a complete remission and ultimately the disease progresses. With these new treatments come higher associated toxicities and significant healthcare costs for the drugs. Proteasome inhibitors are frequently used as one of the treatments for multiple myeloma, with bortezomib (Velcade) approved in 2003 and carfilzomib (Kyprolis- Onyx Pharmaceuticals) approved in July 2012. For several new cancer therapies such as Zelboraf and palkori, companion diagnostics were approved in parallel with the drug to guide physicians in selecting those patients who would benefit from the drug. Unfortunately no such test exists for multiple myeloma, and the associated drug costs and side effects are quite significant. We have discovered a genetic mutation associated with the response to bortezomib. This would be an extremely useful test for physicians to guide treatment of patients and would be useful to stratify patients in clinical trials for next generatin proteasome inhibitors. The goals of this Phase I proposal are to optimize the test using samples already examined by our academic collaborator and develop positive and negative controls for this assay. We also propose to sequence the region involved in this translocation to better understand the disease. Future work envisioned in a Phase II would be to increase the number of clinical samples and sites, test for utility in guiding use of other proteasome inhibitors, and expand into other cancers where proteasome inhibitors have been approved or are in clinical trials. Successful development of this assay would have commercial significance, reduce the cost of health care, and provide benefit to patients while increasing the success in the drug development industry with better selection of patients in clinical trials.